Specific pulmonary lesions may be produced in experimental animals by exposure to the gases oxygen or ozone or by administration of a chemical, paraquat. These lesions, which result from these 3 model compounds, all follow a similar histopathological pattern of development and are thought to result from oxidant-mediated damage to pulmonary membranes and/or pulmonary surfactant. A specific pulmonary enzyme complex which is directly involved in pulmonary lipid metabolism, the microsomal cytochrome b5-dependent fatty acid desaturase system, will be examined for its possible role in the development of the lesion caused by these compounds. This enzyme complex will also be evaluated for its possible utility as an index of acute, oxidant-induced pulmonary damage to the expression of the chronic lesion. A second microsomal enzyme system, the cytochrome P-450 dependent drug metabolizing system, will be simultaneously examined under all experimental conditions. This procedure will establish whether observed results are specific to the lipid desaturase system or are a general effect of the chemicals on pulmonary, microsomal mixed function oxidases. The role of two toxic metabolic intermediates, which may be generated microsomally from each of these model compounds, superoxide anion radical (O2-) and peroxide (O2 ion), and also their respective catabolic enzymes, superoxide dismutase, will be examined for possible common involvement in the production of the characteristic lesion from each of the 3 model systems. Protection against the development of these lesion will also be investigated by altering in vivo levels of the various enzyme system. This project is designed to investigate: 1) The possibility of a common chemical mechanism responsible for the pulmonary lesions resulting from exposure of animals to exygen, ozone, or paraquat. 2) The role of pulmonary fatty acid desaturation in the development of these lesions. 3) Identification of factors useful in design of rational therapy for the chronic lesion associated with acute exposure to these and other strong oxidants.